ULTRASTRUCTURAL EVIDENCE FOR THE FORMATION OF AMYLOID FIBRILS WITHIN CARDIOMYOCYTES IN ISOLATED ATRIAL AMYLOID

Isolated atrial amyloid (IAA) frequently affects elderly human hearts in which only the atria are involved by the deposits. Biochemical anal ysis has indicated that the major subunit protein of IAA is alpha-huma n atrial natriuretic peptide (alpha-ANP), which is synthesized by the atrial muscle cells. To define the exact location of the formation of IAA fibrils, right atria from 25 patients undergoing cardiac surgery h ave been examined by an immunohistochemistry and immunoelectron micros copy with anti-alpha-ANP, apolipoprotein E, amyloid P component, trans thyretin, and cathepsin B antisera. Of 25 patients, 19 were involved w ith IAA deposits which reacted with anti-alpha-ANP, apolipoprotein E, amyloid P component antisera but not with anti-transthyretin antiserum . In 8 of them, amyloid fibrils were seen not only in the interstitium of the atrial myocardium but also in the dilated transverse tubules o f the cardiomyocytes. In some cardiomyocytes, amyloid fibrils were als o demonstrated within the organelles such as coated and uncoated secre tory vesicles or lysosomes. These findings lead to the inescapable con clusion that the polymerization of amyloid fibrils in IAA occurs withi n the cytoplasm of cardiomyocytes under some conditions.